The etiology and pathogenesis of experimental hypertension is being investigated with emphasis on the interaction between genetic determinants and modifying environmental factors. This research program originated with the observations that salt (NaCL) intake could modify blood pressure in both men and rats. Selective breeding produced two lines of rats with opposite, genetically determined blood pressure responses to the same NaCl intake. These two lines were equally sensitive or resistant to other hypertensinogenic stimuli as well. The genetic substrate was therefore assumed to operate in all "forms" of hypertension. Our major objective is now to elucidate the nature of the factors critical in determining the differences in susceptibility to hypertension. To better control the genetic variable involved, we are inbreeding the Dahl hypertension-resistant (R) and hypertension-sensitive (S) rats to develop genetically homozygous animals within each line. In addition, we will continue to determine whether the antihypertensive effect of R renal homografts and the prohypertensive effect of S renal homografts is effective in established renal hypertension. We also propose to study a) the role of the gonads in cadmium-induced hypertension; and b) the effects of acute and chronic cadmium exposure on biochemical and physiological parameters.